I. Longitudinal Studies of Type 2 Personality In Nonhuman Primates: Follow-up of Middle-Aged Males As an investigation of Type 2 personality in nonhuman primates, beginning in 1989, we initiated a study of 104 rhesus juvenile males with varying CSF 5-HIAA concentrations. Our first samples were taken when the subjects were yearlings, still living with their mothers. The subjects have all since migrated from their natal family troop and had varied life histories. Ten years later, in the first study to longitudinally follow male rhesus from childhood through the middle-aged period of life, interesting data have emerged suggesting that the varying life history behavior patterns of individual males are consistent across time and are predicted by differences in CNS monoamine functioning early in life. 1. Continued longitudinal analyses of these males with low monoamine turnover strongly suggest that violent behavior is a life-long pattern, with both low CSF 5-HIAA concentrations, and high levels of aggression early in life predicting violent behavior in these males ten years later, as middle aged adults. 2. While our previous studies have found correlations with serotonin, for the first time our analyses show that independent of the behavior correlations with serotonin, dopamine is also correlated with the behaviors seen in these males. Both HVA and 5-HIAA were correlated with social dominance rank, with high ranking males exhibiting both low CSF HVA and 5-HIAA concentrations. 3. Males leave their natal family troop, generally sometime late in adolescence or early adulthood. When the subject population was subdivided into early migrators (during adolescence prior to maturity) and late migrators (fully mature adults), in the late migrators, there was a negative correlation between CSF HVA and age showing that males with low CSF HVA levels migrated at an earlier age than the adult males who had high CSF HVA. This was interpreted as possibly being mediated by dopamine-mediated sensation seeking, with males high in sensation seeking being more motivated to migrate during the mating season. 4. As the animals age, more have died. With an increased sample size, it remains clear that the male monkeys with low CSF 5-HIAA concentrations die at earlier ages than the monkeys with high CSF 5-HIAA concentrations. II. Studies of Females with Low CSF 5-HIAA concentrations in Feral Environments Unlike males, who live much of their lives independent of family relationships females live in closely bonded, extended families. To assess the phenotype in females, four years ago, we began to gather a sample of young female macaques with varying levels of CSF 5-HIAA. As with males, the females possessing diminished CSF 5-HIAA concentrations engaged in impulsive risk-taking as determined by an analysis of spontaneous arboreal leaping from dangerous heights. The percent of leaps that traversed long distances at dangerous heights were negatively correlated with CSF 5-HIAA. Females with low CSF 5-HIAA concentrations also engaged in high rates of aggression, however, unlike males, they did not engage in higher rates of escalated aggression, instead it was only the low level types of aggression associated with defense of status than do their high CSF 5-HIAA counterparts. CSF HVA concentrations were also found to be significantly negatively correlated with less severe types of aggression and the rate of long, dangerous leaps. CSF MHPG concentrations were associated only with the rate of leaps, and showed no significant correlation with the frequency of aggression. In addition, plasma cortisol concentrations were significantly negatively correlated with low levels of aggression. For the male population, rates of death were high and consorting and inseminating female was low in the males with low CSF 5-HIAA concentrations, which presents a paradox: if differential survival and low reproductive rates are present in males with low CSF 5-HIAA concentrations, what maintains the phenotype in the gene pool? One possibility is that the there is differential survival and reproductive rates in the females. In breeding groups within the laboratory, rates of successful pregnancies and maternal behaviors were assessed in females who were breeding for the first time. Females who failed to give birth during this first year had lower CSF 5-HIAA concentrations when compared with their counterparts who gave birth. Among those females who produced offspring, females with low CSF 5-HIAA concentrations were overly protective and restrictive with their infants. Perhaps as a result, infants born to mothers with low CSF 5-HIAA concentrations spent more time in immature clinging when compared to infants born to mothers with high CSF 5-HIAA concentrations. Independent of serotonin effects, those females with high plasma cortisol levels at the start of the study were more often targets of aggressive bouts, and infants of these females spent more time clinging to their mothers than did those of mothers with low plasma cortisol concentrations. Independent of these findings, females with low plasma cortisol concentrations exhibited high rates of aggression. In a collaboration with Drs. Suomi and DeVinney in NICHD, some of these findings were tested in an ongoing study of rhesus monkey mother-offspring pairs living in the species-normative social group maintained in the NICHD's 5-acre field enclosure in Poolesville. CSF samples were collected from mothers when their infants were 3-5 months of age and assayed for 5-HIAA and HVA (a major central dopamine metabolite); the resulting values were then compared with different aspects of maternal behavior recorded when their infants were 1-3, 4-6, and 7-9 months old, respectively. Consistent with our data from the free-ranging monkeys, measures of maternal protectiveness and infant restraint during the latter two time periods, a time when mothers are actively negotiating weaning, were negatively correlated with mothers' 5-HIAA and HVA concentrations, suggesting more difficulties in the mother-infant relationship during stressful periods, such as weaning in mothers with low CNS serotonin functioning. In contrast, measures of two forms of active infant rejection were positively correlated with concentrations of both monoamine metabolites during the latter two time periods, whereas the rate of passive rejections was not significantly related to concentrations of either metabolites during any time period. III. Impaired CNS Hemispheric Specialization A number of studies have shown that alcoholics and alcohol abusers are more likely to show abnormalities of laterality. In the rhesus there is a bias to left-handedness, with subjects showing interindividual differences in their strength of that preference. In our original study reported last year, we found that in adult subjects that live in the laboratory setting, those not showing this typical left bias were more likely as juveniles and adolescents to exhibit low CSF 5-HIAA concentrations and high cortisol, a pattern similar to that found in some human alcoholics. During the past year, these biochemical findings were replicated in our free-ranging population. In addition, males that showed the atypical bias, were more likely to be loners, spending more time alone and seldom receiving grooming from other animals. When challenged, they were more likely to exhibit submissive behavior, and to receive aggression. In what is to our knowledge the first assessment of the relationship between handedness and psychobiology in free-ranging female macaques, we found that the females who exhibit the atypical right bias were more likely to exhibit low CSF 5-HIAA and plasma cortisol concentrations. Behaviorally, they were more likely to act submissively and to receive aggression, particularly low intensity forms of aggression.